I recently discovered the solution to a long-standing drush issue I have been experiencing on Mac OS X. The symptoms of the problem included several mysterious fatal errors that would crop up from time-to-time as well as the fact that I've had to use the --uri=mysite.dev parameter for every local site on my computer.
I finally tracked down the issue to case-sensitivity. On my Mac, I keep all my local sites in the /Users/michael/Sites directory - this is the default directory that comes with OS X, and can be used by the Mac's built-in version of Apache. I use both MAMP Pro (for client sites) and Acquia Dev Desktop (for teaching), and every site I have lives in this directory.
Up until yesterday, whenever I would fire up my Terminal app, I would (by default) be deposited in /Users/michael, so my first order of business would be to do a cd sites/[directory of the site I wanted to work with]. While that worked fine as far as my Mac was concerned, when I then went to run a drush command, I would either get a fatal error (cannot redeclare a function) or drush wouldn't know which site it was in, and I'd be forced to either use a drush alias or the --uri=mysite.dev parameter. It turns out that because drush is (and most *nix-y tools are) case sensitive, it wasn't actually finding my site, hence the need for the --uri=mysite.dev parameter.
The solution is dead simple. When I fire up my Terminal app, I now use cd Sites, with a capital "S" (actually, I just set a new default directory for it). So far (less than 24 hours in), this has solved every single drush issue I had been having.